The per locus plays a central role in the organization and function of the Drosophila biological clock. This gene has been mapped to a 7-kb DNA segment that codes for a 4.5 kb polyA+ RNA. The complete DNA sequence of the per locus has been determined, and this has allowed us to predict the primary structure of the encoded protein. In this proposal, we will extend our analysis as follows: 1) per RNA and protein titres will be assessed in transformed strains producing rhythms with different periodicities. 2) Certain per locus mutations will be physically mapped, and new mutations will be constructed in vitrok and tested for biological activity following transformation. 3) Antibody raised to per peptides will be used to test the hypothesis that per protein is a proteoglycan associated with cell surfaces. 4) The functions of several per-homologous Drosophila genes will be analyzed to determine if they have a role in the Drosophila clock. 5) The per locus is homologous to DNA from vertebrates. Cloned cDNAs from mouse brain that are homologous to per will be examined to see if they encode per-homologous proteins. 6) We will determine how large a fraction of the Drosophila genome is expressed according to a circadian rhythm, and how the per locus influences these rhythms.